Administration of troxerutin improves testicular function and structure in type-1 diabetic adult rats by reduction of apoptosis

Document Type: Original Research Article

Authors

1 Department of physiology, Faculty of medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

2 Student research committee, Tabriz University of Medical Sciences, Tabriz, Iran

3 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

4 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

5 Department of physiology, Faculty of medicine, Tabriz University of Medical Sciences, Tabriz, Iran

6 Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

7 Drug applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract

Objective: The glucose-reducing effects of troxerutin was previously proven. This study was conducted to evaluate troxerutin effect on testicular structure and spermatozoid parameters in type-1 diabetic adult male rats.
Materials and Methods: Fifty male Wistar rats were randomly classified into 5 groups as follows: control (C), troxerutin (T), diabetic (DM), troxerutin-treated DM (DT) and insulin-treated DM (DI). Testicular structure, apoptosis, lipid peroxidation and antioxidant activity, and spermatozoid parameters were assessed 4 weeks after initiation of the interventions.
Results: The results revealed that diabetes caused testicular stereological changes and significantly increased blood glucose level, testicular MDA content and apoptosis but decreased insulin level, testicular GPX activity, and sperm parameters compared to controls (p
Conclusion: Taken together, troxerutin, comparable to insulin, effectively improved DM-induced testicular dysfunction and sperm parameters in diabetic rats and these effects might be mediated through troxerutin’s anti-apoptotic effects.

Keywords

Main Subjects


Adaramoye O, Akanni O, Adesanoye O, Labo-Popoola O, Olaremi O. 2012. Evaluation of toxic effects of metformin hydrochloride and glibenclamide on some organs of male rats. Niger J Physiol Sci, 27: 137-44.

Alipour MR, Khamaneh AM, Yousefzadeh N, Mohammad-nejad D, Soufi FG. 2013. Upregulation of microRNA-146a was not accompanied bydownregulation of pro-inflammatory markers in diabetic kidney. Mol Biol Rep,40:6477-6483.

Amaral S, Moreno AJ, Santos MS, Seiça R, Ramalho-Santos J. 2006. Effects of hyperglycemia on sperm and testicular cells of Goto-Kakizaki and streptozotocin-treated rat models for diabetes. Theriogenology, 66:2056-2067.

Aybek H, Aybek Z, Rota S, Şen N, Akbulut M. 2008. The effects of diabetes mellitus, age, and vitamin E on testicular oxidative stress. Fertil Steril, 90:755-760.

Badalzadeh R, Layeghzadeh N, Alihemmati A, Mohammadi M. 2015. Beneficial effect of troxerutin on diabetes-induced vascular damages in rat aorta: histopathological alterations and antioxidation mechanism. Int J Endocrinol Metab,13: e25969.

Ballester J, Muñoz MC, Domínguez J, Rigau T, Guinovart JJ, RodríguezGil JE. 2004. Insulindependent diabetes affects testicular function by FSHand LHlinked mechanisms. J Androl, 25:706-719.

Choi WS, Kwon OS, Cho SY, Paick JS, Kim SW. 2015. Effect of chronic administration of PDE5 combined with glycemic control on erectile function instreptozotocininduced diabetic Rats. J Sex Med,12:600-610.

ElangovanP, Jalaludeen A, Ramakrishnan R, Pari L. 2016. Protective Effect of Troxerutin on Nickel-Induced Testicular Toxicity in Wistar Rats. J Environ Patholtoxicol Oncol, 35:133-146.

FanS-h, Zhang Z-f, Zheng Y-l, Lu J, Wu D-m, Shan Q, Hu B, Wang YY. 2009. Troxerutin protects the mouse kidney from d-galactose-caused injury through anti-inflammation and anti-oxidation. Int Immunopharmacol,9:91-96.

Farajdokht F, Amani M, Bavil FM, Alihemmati A, Mohaddes G, Babri S. 2017. Troxerutin protects hippocampal neurons against amyloid beta-induced oxidative stress and apoptosis. EXCLI, 16:1081–1089.

Geetha R, Priya CS, Anuradha CV. 2017. Troxerutin abrogates mitochondrial oxidative stress and myocardial apoptosis in mice fed calorie-rich diet. Chembiol Interac, 278:74-83.

Geetha R, Yogalakshmi B, Sreeja S, Bhavani K, Anuradha CV. 2014. Troxerutin suppresses lipid abnormalities in the heart of high-fat–high-fructose diet-fed mice. Mol cellBiochem,387:123-134.

Jangir RN, Jain GC. 2014. Diabetes mellitus induced impairment of male reproductive functions: a review.Curr Diabetes Rev, 10:147-157.

Kanter M, Aktas C, Erboga M. 2012. Protective effects of quercetin against apoptosis and oxidative stress in streptozotocin-induced diabetic rat testis. Foodchem Toxicol, 50:719-725.

Karimi J, Goodarzi M, Tavilani H, Khodadadi I, Amiri I. 2011. Relationship between advanced glycation end products and increased lipid peroxidation in semen of diabetic men. Diabetes ResClin Pract,91:61-66.

Kianifard D, Sadrkhanlou RA, Hasanzadeh S. 2012. The ultrastructural changes of the sertoli and leydig cells following streptozotocin induced diabetes. Iran JBasic Med Sci, 15:623-635.

Keyhanmanesh R, Hamidian GR, Alipour MR, Ranjbar M,Oghbaei H. 2018. Protective effects of sodium nitrate against testicular apoptosis andspermatogenesis impairments in streptozotocin-induced diabetic male rats.Life Sciences, 211: 63–73.

Liu C-M, Ma J-Q, Lou Y. 2010. Chronic administration of troxerutin protects mouse kidney against D-galactose-induced oxidative DNA damage. Food Chem Toxicol, 48:2809-2817.

Lu J, Wu D-m, Zheng Z-h, Zheng Y-l, HuB, Zhang Z-f. 2011. Troxerutin protects against high cholesterol-induced cognitive deficits in mice. Brain,134:783-797.

Mokhtari B, Badalzadeh R, Alihemmati A, Mohammadi M. 2015. Phosphorylation of GSK-3β and reduction of apoptosis as targets of troxerutin effect on reperfusion injury of diabetic myocardium. Eur JPharmacol, 765:316-321.

Naderi R, Mohaddes G, Mohammadi M, Ghaznavi R, Ghyasi R, Vatankhah AM. 2015. Voluntary Exercise Protects Heart from Oxidative Stress in Diabetic Rats. Adv Pharm Bull, 5: 231-236.

Nakayama Y, Yamamoto T, Abe S-I. 2004. IGF-I, IGF-II and insulin promote differentiation of spermatogonia to primary spermatocytes in organ culture of newt testes. Int J Develop Biol,43:343-347.

Oghbaei H, Alipour MR, Hamidian GR, Ahmadi M, Ghorbanzadeh V, Keyhanmanesh R. 2018. Two months sodium nitrate supplementation alleviates testicular injury in streptozotocin-induced diabetic male rats. Exp Physiol, 103: 1603-1617.

Olfati A, Moghadam GH, Baradaran B, Hamidian GH. 2018. The effect of estradiol benzoate and FSH on hormonal levels and stereology structure of testis in Ghezel lambs treated with Tamoxifen citrate. Revue Med Vet, 169: 58-64.

Oliveira P, Alves M, Rato L, Laurentino S, Silva J, Sa R, Barros A, Sousa M, Carvalho RA, Cavaco JE, Socorro S. 2012. Effect of insulin deprivation on metabolism and metabolism-associated gene transcript levels of in vitro cultured human Sertoli cells. Biochim Biophys Acta,1820:84-89.

Perumal E, Jalaludeen AM, Ramakrishnan R, Amutha K, Pari L. 2017. In vivo andIn vitro antioxidant activity of troxerutin on Nickel induced toxicity in experimental Rats.Iran J Pharm Res, in press.

Pourmemar E, Majdi A, Haramshahi M, Talebi M, Karimi P, Sadigh-Eteghad S. 2017. Intranasal cerebrolysin attenuates learning and memory impairments in D-galactose-induced senescence in mice. Exp Gerontol, 87:16-22.

Sampath S, Karundevi B. 2014. Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic adult male rat. Mol Cell Biochem,395:11-27.

Shokri S, Aitken RJ, Abdolvahhabi M, Abolhasani F, Ghasemi FM, Kashani I, Ejtemaeimehr S, Ahmadian S, Minaei B, Naraghi MA, BarbarestaniM. 2010. Exercise and supraphysiological dose of nandrolone deconoate increase apoptosis in spermatogenic cells. Basic Clin Pharmacol Toxicol, 106: 324-330.

Vinothkumar R, Kumar RV, Sudha M, Viswanathan P, Balasubramanian T, Nalini N. 2014. Modulatory effect of troxerutin on biotransformingenzymes and preneoplasic lesions induced by 1, 2-dimethylhydrazine in rat colon carcinogenesis. Expmol Pathol, 96:15-26.

Wang H, Yang L-L, Ji Y-L, Chen Y-H, Hu J, Zhang C, Zhang J, Xu DX . 2016. Different fixative methods influence histological morphology and TUNEL staining in mouse testes. Reprod Toxicol, 60:53-61.

Yu Y, ZhengG. 2017. Troxerutin protects against diabetic cardiomyopathy through NFκB/AKT/IRS1 in a rat model of type 2 diabetes. Mol Med Rep,15:3473-3478.

Zavvari Oskuye Z, Mirzaei Bavil F, Hamidian GR, Mehri K, Qadiri A, Ahmadi M, Ogbaei H, Vatankhah AM, Keyhanmanesh R. 2019. The effect of troxerutin on male fertility in prepubertal type 1 diabetic male rats. Iran J Basic Med Sci, 22:197-205.

Zhang Z, Wang X, Zheng G, Shan Q, Lu J, Fan S, Sun C, Wu D, Zhang C, Su W, Sui J, Zheng Y. 2017. Troxerutin attenuates enhancement of hepatic gluconeogenesis by inhibiting NOD activation-mediated inflammation in high-fat diet-treated mice. Int JMol Sci,18:31-46.

Zhao Y, Tan Y, Dai J, Li B, Guo L, Cui J, Wang G, Shi X, Zhang X, Mellen N, Li W, Cai L.2011. Exacerbation of diabetes-induced testicular apoptosis by zinc deficiency is most likely associated with oxidative stress, p38 MAPK activation, and p53 activation in mice. Toxicol Lett, 200:100-106.